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RV Septal Versus Minimized RV Pacing in Sick Sinus Syndrome

Conditions
Sick Sinus Syndrome
Interventions
Procedure: pacemaker implantation, AAI(R)-DDD(R) versus DDD(R)
Registration Number
NCT01477138
Lead Sponsor
Klinikum Nürnberg
Brief Summary

Background:

* Potential negative effects of pacing in the RV-apex are well documented

* However, study results comparing septal / RVOT-pacing versus RV-apical pacing controversial.

* The optimal pacing mode in SSS (DDDR versus AAIR) is unclear, as the DDD (R) mode with an AV delay ≤ 220 ms should be the preferred pacing mode, according to the DANPACE trial \[DANPACE, ESC 2010, Stockholm\].

Aim:

- to evaluate chronic effects of proven right ventricular septal compared to minimized right ventricular septal pacing in patients with SSS

Inclusion criterion:

-Pacemaker indication according to current guidelines: sick sinus syndrome (SSS)

Exclusion criteria:

* Life expectancy \< 2 years

* Age \<18 years

* Noncompliance with regard to participation in the study

* Pregnancy

* AV block ° 2 and higher

* Permanent atrial fibrillation

* Heart failure NYHA III and IV, reduced LV-EF \<40%

* ICD indication

* Acute coronary syndrome. PCI or CABG \<3 months

* Heart transplant

* Placement of septal RV electrode is not possible

Study design:

* Prospective, monocentric, randomized, double-blinded

* Run-in phase: for weeks AAI \[R\]-DDD \[R\]

* Randomization: two groups A) septal right ventricular chamber pacing: mode DDD \[R\] versus B) Reduction of unnecessary ventricular pacing: AAI \[R\]-DDD \[R\].

* FU: 6 and 12-months

Primary endpoints:

-LV ejection fraction and end-systolic LV volume after 12 months.

Secondary endpoints:

-LV end-diastolic volume, TAPSE, parameters of dyssynchrony (SPWMD, LV-PEP, IVMD), AF-burden, % ventricular pacing, CPX: peak oxygen consumption (peak VO2), VO2 AT, VO2/HR, VE/VCO2 slope; QoL scores (SF-36) after 12 months.

Statistics/sample size estimation:

In order to detect a difference in LVEF of 5% and for LV-ESV of 5 mL between the 2 groups after 12 months:

* 90% power/alpha 5%: 84 patients per group

* 80% power/alpha 5%: 63 patients per group

* 10% for compensation of drop-outs / patients lost of follow-up. Two-sided 5% type 1 error Analysis intention-to-treat and based on the finally programmed pacing mode.

Material

* PG: market released dual chamber pacemakers with the ability to pace AAI(R) -DDD(R)

* pacing leads: market-released standard active electrodes

* RV electrode: septal verified under multi-level screening (RAO/LAO) and ECG (LBBB narrow \<150 ms / inferior axis)

Detailed Description

Background:

* Potential negative effects of pacing in the RV-apex are well documented

* Asynchronous ventricular activation

* reduction of systolic and diastolic LV function

* Experimental data: histological changes

* Asymmetric LV hypertrophy and thinning

* However, study results comparing septal / RVOT-pacing versus RV-apical pacing controversial:

* Acute versus chronic

* Small number of cases, uncontrolled, unblinded,

* Brief periods of observation in the cross-over design (3 months)

* "RVOT" often summarizes different stimulation sites: high RVOT, lateral, septal. Actually only limited data with proven septal stimulation

* No objective performance assessment (CPX)

* Assessment of alternative stimulation site previously RVOT versus RV-apex,

* ventricular pacing compared to ventricular pacing, then tested a potential harm to another

* The question of the optimal pacing mode of patients with SSS (DDDR versus AAIR) appears to be open again. While in Germany, two-chamber systems with AAI \[R\] mode with ventricular back-up are used, should the DDD (R) mode with an AV delay ≤ 220 ms be the preferred pacing mode, according to the results of the DANPACE trial for patients with SSS \[DANPACE, ESC 2010, Stockholm\].

Aim:

- to evaluate chronic effects of proven right ventricular septal compared to minimized right ventricular septal pacing in patients with SSS

Inclusion criterion:

-Pacemaker indication according to current guidelines: sick sinus syndrome (SSS)

Exclusion criteria:

* Life expectancy \< 2 years

* Age \<18 years

* Noncompliance with regard to participation in the study

* Pregnancy

* AV block ° 2 and higher

* Permanent atrial fibrillation

* Heart failure NYHA III and IV, reduced LV-EF \<40%

* ICD indication

* Acute coronary syndrome. PCI or CABG \<3 months

* Heart transplant

* Placement of septal RV electrode is not possible

Study design:

* Prospective, monocentric, randomized, double-blinded

* Run-in phase: 4 weeks AAI \[R\]-DDD \[R\]

* ECG, PM-interrogation, echocardiography, performance diagnostics, CPX, QoL questionnaire

* Randomization: two groups 4 weeks (between 3 to 6 weeks) after implant A) septal right ventricular chamber pacing: mode DDD \[R\] versus B) Reduction of unnecessary ventricular pacing: AAI \[R\]-DDD \[R\].

* FU: 6 and 12-months

* ECG, Holter-ECG, PM-interrogation, echocardiography, performance diagnostics, CPX, QoL questionnaire

* Extension of follow-up if possible

Primary endpoints:

-LV ejection fraction and end-systolic LV volume after 12 months.

Secondary endpoints:

-LV end-diastolic volume, TAPSE, parameters of dyssynchrony (SPWMD, LV-PEP, IVMD), AF-burden, % ventricular pacing, CPX: peak oxygen consumption (peak VO2), VO2 AT, VO2/HR, VE/VCO2 slope; QoL scores (SF-36) after 12 months.

Blinding:

* Patient compared to the pacing mode

* Physician: offline analysis of echo and CPX blinded to the pacing mode

Statistics/sample size estimation:

In order to detect a difference in LVEF of 5% and for LV-ESV of 5 mL between the 2 groups after 12 months:

* 90% power/alpha 5%: 84 patients per group

* 80% power/alpha 5%: 63 patients per group

* 10% for compensation of drop-outs / patients lost of follow-up. Two-sided 5% type 1 error Analysis intention-to-treat and based on the finally programmed pacing mode.

Material

* PG: market released dual chamber pacemakers with the ability to pace AAI(R) -DDD(R)

* pacing leads: market-released standard active electrodes (eg. BSCI FineLine 4470 and 4471) Implantation

* Transvenously

* RA-electrode: if possible, short atrial conduction time

* RV electrode: septal verified under multi-level screening (RAO/LAO) and ECG (LBBB narrow \<150 ms / inferior axis)

Recruitment & Eligibility

Status
UNKNOWN
Sex
All
Target Recruitment
126
Inclusion Criteria
  • Pacemaker indication according to current guidelines: sick sinus syndrome (SSS)
Exclusion Criteria
  • Life expectancy <2 years
  • Age < 18 years
  • Noncompliance with regard to participation in the study
  • Pregnancy
  • AV block ° 2 and higher
  • Permanent atrial fibrillation
  • Heart failure NYHA III and IV, reduced LV-EF < 40%
  • ICD indication
  • Acute coronary syndrome. PCI or CABG < 3 months
  • Heart transplant
  • Placement of septal RV electrode is not possible

Study & Design

Study Type
OBSERVATIONAL
Study Design
Not specified
Arm && Interventions
GroupInterventionDescription
DDD(R)pacemaker implantation, AAI(R)-DDD(R) versus DDD(R)SSS. PM programmed to DDD(R) mode with ventricular pacing on the right ventricular septum.
AAI(R)<=>DDD(R)pacemaker implantation, AAI(R)-DDD(R) versus DDD(R)SSS, PM-mode programmed for minimizing right ventricular pacing on the right interventricular septum
Primary Outcome Measures
NameTimeMethod
end-systolic LV volumeat randomisation and after 12 months
left ventricular ejection fraction (LV-EF)at randomisation and after 12 months

TTE, Simpson, biplane

Secondary Outcome Measures
NameTimeMethod
TAPSEat randomisation and after 12 months
echocardiographic parameter of dyssynchronyat randomisation and after 12 months

TTE, SPWMD, LV-PEP, IVMD

peak VO2, VO2 AT, VO2/HR, VE/VCO2 slopeat randomisation and after 12 months

CPX: cardiopulmonary exercice testing

quality of life-scoresat randomisation and after 12 months

SF-36

AF burdenat randomisation and after 12 months
% ventricular pacingat randomisation and after 12 months
LV end diastolic volumeat randomisation and after 12 months

TTE

Trial Locations

Locations (1)

Klinikum Nuernberg South

🇩🇪

Nuernberg, Bavaria, Germany

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